Targeted Treatment of Obstructive Sleep Apnea to Reduce Cardiovascular Disparity

阻塞性睡眠呼吸暂停的靶向治疗以减少心血管差异

• 批准号: 8811333
• 负责人: Bharati Prasad
• 金额: --
• 依托单位: JESSE BROWN VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8811333
• 关键词: Adherence; Admixture; African; African American; Aftercare; Age; American; Apnea; Appointment; Area; Award; Biological; Biological Factors; Biological Markers; Biomedical Research; Blood Pressure; Body mass index; Breathing; Cardiovascular Diseases; Cardiovascular system; Caring; Catecholamines; Chicago; Clinical; Clinical Sciences; Consensus; Continuous Positive Airway Pressure; Critical Care; Data; Data Analyses; Demographic Factors; Development Plans; Doctor of Philosophy; European; Excessive Daytime Sleepiness; Foundations; France; Funding; Future; General Population; Genetic; Genotype; Goals; Health; Heterogeneity; High Prevalence; Hospitals; Hour; Hypertension; Illinois; Individual; International; Intervention; Intervention Trial; Isoprostanes; K-Series Research Career Programs; Knowledge; Lung; Measurement; Measures; Medicine; Mentors; Mentorship; Morbidity - disease rate; Newly Diagnosed; Obesity; Obstructive Sleep Apnea; Other Genetics; Outcome; Outcome Assessment; Oxidative Stress; Pathogenesis; Patients; Physicians; Population; Population Heterogeneity; Public Health; Relative (related person); Research; Resources; Retrospective Studies; Risk; Role; Scientist; Severities; Sleep; Societies; Sympathetic Nervous System; Symptoms; Testing; United States Department of Veterans Affairs; Universities; Upper arm; Vascular Diseases; Veterans; abstracting; base; blood pressure reduction; brachial artery; career; career development; craniofacial; design; experience; high risk; hypertension control; improved; indexing; multidisciplinary; novel; patient population; premature; professor; programs; prospective; research and development; response; targeted treatment; treatment response; urinary; vigilance

DESCRIPTION (provided by applicant): The candidate for this Clinical Science Research and Development Career Development Award (CDA2) is Bharati Prasad, MD, MS, a pulmonary, critical care, and sleep medicine staff physician at Jesse Brown VAMC. Dr. Prasad's academic appointment is as a tenure-track Assistant Professor at the University of Illinois at Chicago (UIC). Dr. Prasad's long-term career goals are to become an independent physician-scientist developing effective strategies to reduce cardiovascular disease (CVD) in diverse populations through interventions that optimize sleep and breathing. To achieve her goals, Dr. Prasad has assembled a comprehensive career development plan and a strong team of mentors with longstanding VA and other federal funding and mentorship experience. Her primary mentor, Frances M. Weaver PhD, is a VA Research Career Scientist and an experienced clinical trialist. Her co- mentors are David W. Carley, PhD (an expert in autonomic derangements associated with Obstructive Sleep Apnea; OSA and developing novel treatment interventions for OSA) and Samuel T. Kuna, MD, with expertise in Continuous Positive Airway Pressure (CPAP) treatment intervention trials in patients with OSA and an extensive research record in the VA. The proposal also includes a multidisciplinary team of collaborators with expertise in the areas of measurement of biomarkers key to the pathogenesis of hypertension in OSA, genetic ancestry in biomedical research, early non-invasive assessment of vascular dysfunction, and longitudinal data analyses. The proposal leverages the extensive research and clinical resources at Jesse Brown VAMC, including a large pool of diverse Veteran populations served. Obstructive Sleep Apnea (OSA) and hypertension are both common and severe problems in African American individuals (as noted in the International Society on Hypertension in Blacks consensus statement). CPAP treatment of OSA is effective in controlling hypertension in patients with OSA, but has not been studied in African Americans, a high-risk population with potentially large health gains. This is an area of significance because poorly controlled hypertension leads to progression of CVD and morbidity in this population. By identifying CPAP treatment-response and relevant moderators of this response in African Americans with hypertension and OSA, targeted treatment of OSA can be implemented, reducing the excess burden of CVD. We will determine the relative magnitude of hypertension response to CPAP treatment (ambulatory blood pressure and central aortic blood pressure) in 220 African American and European American Veterans with hypertension and newly diagnosed OSA (specific aim 1). We will measure changes in pathogenic biomarkers (urinary cumulative sympathetic nervous system activity and oxidative stress) that are responsive to CPAP treatment in addition to hypertension assessments. Further, we will examine the role of excessive daytime sleepiness (EDS), a potentially important moderator of treatment response, in these two patient populations (specific aim 2). Finally, we will adjust our outcomes assessment for the anticipated biological heterogeneity among self-identified African Americans by measuring genetic ancestry (exploratory aim). This award will provide the foundation for the goals of this research program to reduce CVD disparity in diverse populations with targeted treatment of OSA.

描述（由申请人提供）： 该临床科学研发职业发展奖（CDA2）的候选人是MD，MD的Bharati Prasad，肺部，重症监护和睡眠医学人员的医生，Jesse Brown VAMC的医生。普拉萨德博士的学术任命是伊利诺伊大学芝加哥大学（UIC）的终身助理助理教授。普拉萨德博士的长期职业目标是成为独立的医师科学家，制定有效的策略，通过优化睡眠和呼吸的干预措施来减少不同人群中心血管疾病（CVD）的有效策略。为了实现她的目标，普拉萨德博士召集了一项全面的职业发展计划，并拥有一支由VA和其他联邦资金和指导经验的强大导师团队。她的主要导师Frances M. Weaver博士是VA研究职业科学家和经验丰富的临床试验者。她的合作者是博士学位的David W. Carley（自主神经呼吸呼吸暂停相关的自主神经疾病专家； OSA以及为OSA开发新的治疗干预措施）和医学博士Samuel T. Kuna，具有OSA患者和VA患者的广泛研究记录的连续阳性气道压力（CPAP）治疗试验的专业知识。该提案还包括一个由合作者组成的多学科团队，在测量生物标志物的领域具有专业知识，这是OSA高血压发病机理的关键，生物医学研究中的遗传祖先，早期的血管功能障碍的早期非侵入性评估和纵向数据分析。该提案利用杰西·布朗VAMC的广泛研究和临床资源，其中包括大量的资深人口。阻塞性睡眠呼吸暂停（OSA）和高血压是非裔美国人的常见和严重问题（如黑人共识陈述中国际高血压学会所指出的那样）。 OSA的CPAP治疗可有效控制OSA患者的高血压，但尚未在非洲裔美国人中研究，这是一个潜在的健康增长的高风险人群。这是一个重要的领域，因为控制不良的高血压导致该人群中CVD和发病率的发展。通过鉴定患有高血压和OSA的非裔美国人的CPAP治疗响应和这种反应的相关主持人，可以实施针对性的OSA治疗，从而减少CVD的多余负担。我们将在220名非裔美国人和欧美退伍军人中，确定对CPAP治疗的高血压反应的相对大小（门诊血压和中央主动脉血压），具有高血压和新诊断的OSA（特定目标1）。除了高血压评估外，我们还将测量病原生物标志物（尿累积交感神经系统活动和氧化应激）的变化。此外，我们将研究这两个患者人群中过度重要的治疗反应的主持人（EDS）（EDS）的作用（特定目标2）。最后，我们将通过测量遗传血统（探索目的）来调整自我认同的非洲裔美国人的预期生物异质性的结果评估。该奖项将为该研究计划的目标奠定基础，以减少OSA有针对性治疗的不同人群中CVD差异。